In the present study, a nonlocal continuum model based on the Eringen’s theory is developed for vibration analysis of orthotropic nano-plates with arbitrary variation in thickness. Variational principle and Ritz functions are employed to calculate the size dependent natural frequencies of non-uniform nano-plates on the basis of nonlocal classical plate theory (NCLPT). The Ritz functions eliminate the need for mesh generation and thus large degrees of freedom arising in discretization methods such as finite element (FE). Effect of thickness variation on natural frequencies is examined for different nonlocal parameters, mode numbers, geometries and boundary conditions. It is found that thickness variation accompanying small scale effect has a noticeable effect on natural frequencies of non-uniform plates at nano scale. Also a comparison with finite element solution is performed to show the ability of the Ritz functions in fast converging to the exact results. It is anticipated that presented results can be used as a helpful source in vibration design and frequency optimization of non-uniform small scaled plates.